Maximal Recruitment Open Lung Ventilation in Acute Respiratory Distress Syndrome (PHARLAP). A Phase II, Multicenter Randomized Controlled Clinical Trial.
Carol L HodgsonD James CooperYaseen ArabiVictoria KingAndrew BerstenShailesh BihariKathy BrickellAndrew DaviesCiara FaheyJohn FraserShay McGuinnessLynne MurrayRachael ParkeEldho PaulDavid TuxenShirley VallanceMeredith YoungAlistair NicholPublished in: American journal of respiratory and critical care medicine (2020)
Rationale: Open lung ventilation strategies have been recommended in patients with acute respiratory distress syndrome (ARDS).Objectives: To determine whether a maximal lung recruitment strategy reduces ventilator-free days in patients with ARDS.Methods: A phase II, multicenter randomized controlled trial in adults with moderate to severe ARDS. Patients received maximal lung recruitment, titrated positive end expiratory pressure and further Vt limitation, or control "protective" ventilation.Measurements and Main Results: The primary outcome was ventilator-free days at Day 28. Secondary outcomes included mortality, barotrauma, new use of hypoxemic adjuvant therapies, and ICU and hospital stay. Enrollment halted October 2, 2017, after publication of ART (Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial), when 115 of a planned 340 patients had been randomized (57% male; mean age, 53.6 yr). At 28 days after randomization, there was no difference between the maximal lung recruitment and control ventilation strategies in ventilator-free days (median, 16 d [interquartile range (IQR), 0-21 d], n = 57, vs. 14.5 d [IQR, 0-21.5 d], n = 56; P = 0.95), mortality (24.6% [n = 14/56] vs. 26.8% [n = 15/56]; P = 0.79), or the rate of barotrauma (5.2% [n = 3/57] vs. 10.7% [n = 6/56]; P = 0.32). However, the intervention group showed reduced use of new hypoxemic adjuvant therapies (i.e., inhaled nitric oxide, extracorporeal membrane oxygenation, prone; median change from baseline 0 [IQR, 0-1] vs. 1 [IQR, 0-1]; P = 0.004) and increased rates of new cardiac arrhythmia (n = 17 [29%] vs. n = 7 [13%]; P = 0.03).Conclusions: Compared with control ventilation, maximal lung recruitment did not reduce the duration of ventilation-free days or mortality and was associated with increased cardiovascular adverse events but lower use of hypoxemic adjuvant therapies.Clinical trial registered with www.clinicaltrials.gov (NCT01667146).
Keyphrases
- acute respiratory distress syndrome
- respiratory failure
- extracorporeal membrane oxygenation
- mechanical ventilation
- phase ii
- clinical trial
- open label
- double blind
- randomized controlled trial
- phase iii
- study protocol
- heart rate
- placebo controlled
- nitric oxide
- end stage renal disease
- resistance training
- early stage
- cardiovascular events
- ejection fraction
- heart failure
- risk factors
- newly diagnosed
- intensive care unit
- coronary artery disease
- blood pressure
- chronic kidney disease
- prognostic factors
- cystic fibrosis
- minimally invasive
- cross sectional
- emergency department
- peritoneal dialysis
- health insurance
- left ventricular
- type diabetes
- early onset
- patient reported
- body composition
- hiv infected
- patient reported outcomes